Within the NTDU group, we continue to utilize a number of automated, medium throughput assays to screen small compound collections against rat mixed cortical cultures, human neural stem cells (NSC) and human NSC-derived neurons and astrocytes. We've utilized live cell imaging based assays with human neurons, as well as developed fluorescence-based assays to probe high content imaging endpoints. These cell based screening assays, in 384 well plate format, have been successfully employed in multiple screens with multiple investigators. We have continued to generate new chemical tool compounds in our chemistry labs to facilitate screening and mechanistic studies in our research projects. We produce and purify a number of recombinant proteins, such as Cdk5 and the HIV Tat protein for our own studies and provide that Tat protein to extramural researchers around the world for their studies. With the Section of Infections of the Nervous System (SINS), we have continued to work on multiple research projects. We continue to characterize the neurotoxicity resulting from the expression of the HERV-K env protein in NSC and human neurons, and have already identified some compounds which attenuate HERVK env mediated neurotoxicity. We have recently begun to characterize the toxic actions of Zika virus on neural cells, and have identified some compounds which may block the Zika virus-dependent neurotoxicity . The HIV Tat antagonist program has incorporated direct label-free binding assays, including isothermal titration calorimetry, as well as Tat-dependent selective LTR activation assays to complete the screening of more than 2000 compounds to identify new lead Tat inhibitors. The resultant hit compounds continue to be characterized for potency and biopharmaceutical properties. The NTDU has continued a number of studies in collaboration with other intramural investigators. We continue to work with Dr. Harish Pant and his research team to characterize the neuroprotective actions of the Cdk5 modulator TFP-5 against multiple toxic insults. Likewise, we continue to work with the Sibley research group to characterize the dopamine D3 receptor agonists that they have identified, using our live cell imaging platforms for quantitative analysis. We have recently begun working with two clinical investigators, Drs. Kareem Zaghloul and Peter Williamson on new research projects with their respective laboratories. We continue to work closely with the Dr. Francis McMahon laboratory to generate fluorescently labeled NSC and neuronal cultures from control and neuropsychiatric patients, to characterize their morphologic changes in response to stressors or toxic challenges.